In contrast to left ventricular assist devices used in end stage cardiac disease patients, there are few available bridging devices available for end stage lung disease patients. Extracorporeal membrane oxygenation (ECMO) devices have a significant role in short term acute neonatal respiratory diseases and a more limited role in acute adult respiratory diseases. However, ECMO requires hospitalization in critical care units and specialized health care providers. As such, it is not a practical or cost effective option for long term bridging to lung transplant. New innovative cost-effective easily implementable technologies are desperately needed. We have extensively studied ex vivo lung bioengineering with focus on de- and recellularization of mammalian lungs. This includes developing potential transplantation strategies creating ex vivo autologous lungs from decellularized cadaveric or failed donor lungs recellularized with cells obtained from the eventual transplant recipient. This is a powerful rapidly evolving promising approach. However, a number of significant hurdles remain including recapitulating appropriate gas exchange and respiratory physiology. As opposed to mammalian lungs, avian lungs are static multilayered structures in which gas exchange occurs by cross current exchange and is more efficient than the more complex ventilation required by mammalian lungs. As such, avian lungs could provide a potentially novel and effective bioscaffold for use as lung assist devices and possibly also in transplantation schemes. The central hypothesis of this proposal therefore is that decellularized avian lungs, recellularized with human lung epithelial, endothelial, and stromal cells, and subsequently with relevant lung stem and progenitor cells, will therefore provide a novel and more powerful gas exchange unit than recellularized mammalian lungs. The recellularized avian lungs could be utilized as independent hospital (ICU)-based units, comparable to ECMO, portable units, comparable to portable dialysis devices or insulin pumps, or as gas exchange units implantable into the thoracic cavity. These objectives will be investigated in the following Specific Aims: 1. To fully characterize de- and recellularization of representative avian lungs. 2. To develop initial technologies for novel Avian Lung Assist Devices (ALAD) incorporating recellularized avian lungs that could be potentially utilized for independent, portable, or implantable lung assist devices. The aims will be pursued in collaboration between lung biologist Daniel Weiss and engineers Patrick Lee and Dryver Huston. The intellectual property and technology developed from these studies will be subsequently licensed for further industry-based development.